Abstract：
OBJECTIVE: The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co-ordination centre that controls a wide range of vascular functions including the regulation of blood pressure and blood flow. To co-ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved.
METHODS: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels.
RESULTS: Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3-induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C-dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation.
CONCLUSIONS: These results show that signalling switches underlie endothelial cell-to-cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.
METHODS: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels.
RESULTS: Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3-induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C-dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation.
CONCLUSIONS: These results show that signalling switches underlie endothelial cell-to-cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.
摘要：
目的：单层细胞覆盖所有血管，内皮，是一个复杂的信号协调中心，控制广泛的血管功能，包括血压和血流的调节。为了协调活动，细胞间的通讯是组织水平反应出现所必需的。虽然细胞之间的信号传播是一种重要的通信形式，在完整内皮中的传播机制尚未解决。
方法：精确信号产生和靶向细胞操作与完整血管内皮中的高时空中尺度Ca2成像结合使用。
结果:多种机制维持通信,使得Ca2+波传播发生,而与小区之间的连接状态无关。在相邻的细胞之间，再生IP3诱导的IP3产生传递Ca2信号，并解释了伴随组织活动的血流增加的基础上的血管舒张。肌醇肽本身足以在偶联的细胞中引起再生的磷脂酶C依赖性Ca2波。没有任何间隙连接，需要Ca2+扩散或细胞外信使的释放来支持这种类型的细胞间Ca2+信号传导。相比之下,当细胞之间存在不连续性时，作为可扩散的细胞外信使释放的ATP通过不连续传递Ca2信号并驱动传播的血管舒张。
结论：这些结果表明，信号转换是内皮细胞到细胞信号传递的基础，并揭示了在内皮损伤面前如何维持通信。这些发现为理解内皮中的波传播和细胞信号提供了新的框架。
方法：精确信号产生和靶向细胞操作与完整血管内皮中的高时空中尺度Ca2成像结合使用。
结果:多种机制维持通信,使得Ca2+波传播发生,而与小区之间的连接状态无关。在相邻的细胞之间，再生IP3诱导的IP3产生传递Ca2信号，并解释了伴随组织活动的血流增加的基础上的血管舒张。肌醇肽本身足以在偶联的细胞中引起再生的磷脂酶C依赖性Ca2波。没有任何间隙连接，需要Ca2+扩散或细胞外信使的释放来支持这种类型的细胞间Ca2+信号传导。相比之下,当细胞之间存在不连续性时，作为可扩散的细胞外信使释放的ATP通过不连续传递Ca2信号并驱动传播的血管舒张。
结论：这些结果表明，信号转换是内皮细胞到细胞信号传递的基础，并揭示了在内皮损伤面前如何维持通信。这些发现为理解内皮中的波传播和细胞信号提供了新的框架。
